Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases

BACKGROUND Evaluating the psychological resilience of lung cancer(LC)patients helps understand their mental state and guides future treatment.However,there is limited research on the psychological resilience of LC patients with bone me-tastases.AIM To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience.METHODS LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University.The psychological scores of the enrolled patients were collected.They were then grouped based on the mean psychological score:Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group.The baseline data(age,gender,education level,marital status,residence,monthly income,and religious beliefs),along with self-efficacy and medical coping mode scores,were compared.RESULTS This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023,with an average psychological resilience score of 63.24±9.96 points.After grouping,the low-score group consisted of 69 patients,including 42 males and 27 females,with an average age of 67.38±9.55 years.The high-score group consisted of 73 patients,including 49 males and 24 females,with a mean age of 61.97±5.00 years.χ2 analysis revealed significant differences between the two groups in education level(χ2=6.604,P=0.037),residence(χ2=12.950,P=0.002),monthly income(χ2=9.375,P=0.009),and medical coping modes(χ2=19.150,P=0.000).Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores(t=3.383,P=0.001)and lower age than the low-score group(t=4.256,P<0.001).Furthermore,multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience[odds ratio(OR)=0.926,P=0.035,95%confidence interval(CI):0.862-0.995],while age(OR=1.099,P=0.003,95%CI:1.034-1.169)and medical coping modes(avoidance vs confrontation:OR=3.767,P=0.012,95%CI:1.342-10.570;resignation vs confrontation:OR=5.687,P=0.001,95%CI:1.974-16.385)were identified as independent risk factors.A predictive model based on self-efficacy,age,and medical coping modes was developed.The receiver operating characteristic analysis showed an area under the curve value of 0.778(95%CI:0.701-0.856,P<0.001),indicating that the model has good predictive performance.CONCLUSION LC patients with bone metastases are less psychologically resilient than the general population.Factors such as self-efficacy,age,and medical coping modes influence their psychological resilience.Patients with low self-efficacy,old age,and avoidance/resignation coping modes should be closely observed.

Bone metastases:When and how lung cancer interacts with bone

Bone metastasis is a common and debilitating consequence of lung cancer:30%-40% of patients with nonsmall cell lung cancer develop bone metastases during the course of their disease. Lung cancer cells find a favorable soil in the bone microenvironment due to factors released by the bone matrix, the immune system cells, and the same cancer cells. Many aspects of the cross-talk among lung tumor cells, the immune system,and bone cells are not clear, but this review aims to summarize the recent findings in this field, with particular attention to studies conducted to identify biomarkers for early detection of lung cancer bone metastases.

31inical features and prognostic factors for patients wilh bone metastases from prostate cancer

To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer （PCa）. We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009. The overall survival rate after bone metastases was calculated using the Kaplan-Meier method. The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models. The follow-up rate was 100%, the follow-up cases during 1, 3 and 5 years were 103, 79 and 55, respectively. The 1-, 3- and 5-year survival rates were 89.1%, 60.9% and 49.8%, respectively, with a median survival time of 48.5 months for patients with bone metastases from PCa. In univariate analysis, age, Gleason score, clinical stage, the number of bone lesions, alkaline phosphatase （ALP） level, invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis. By multivariate analysis using Cox regression, ALP level, Gleason score and non-regional lymph node metastases were independent prognostic factors. These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

Bone metastases from hepatocellular carcinoma:clinical features and prognostic factors

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

Targeting mast cells in gastric cancer with special reference to bone metastases

Bone metastases from gastric cancer(GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells(MCs) positive to tryptase(MCPT) in primary gastric tumor angiogenesis. Recently,we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating,peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents,such as MCs tryptase inhibitors(gabexate mesylate,nafamostat mesylate) or c-KitR tyrosine kinase inhibitors(imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patientsaffected by bone metastases.

Bone metastases as initial presentation of hepatocellular carcinoma

Extra-hepatic spread is present in 5% to 15% of patients with hepatocellular carcinoma(HCC) at the time of diagnosis. The most frequent sites are lung and regional lymph nodes. Here, we report 3 cases of unsuspected HCC with symptoms due to bone lesions as initial presentation. Morphological characteristics and immunohistochemistry from the examined bone were the key data for diagnosis. None of the patients had an already known chronic liver disease. Differential diagnoses with HCC upon ectopic liver disease or hepatoid adenocarcinoma were shown. Therapy with the orally active multikinase inhibitor sorafenib plus symptomatic treatment was indicated.

Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

The efficacy of ^(89)Sr combined with ^(99)Tc-MDP in the treatment of the advanced breast cancers with bone metastases

Objective： The aim of our study was to evaluate the efficacy of 89Sr combined with Technetium [^99Tc] Methylene- diphosphonate Injection （^99Tc-MDP） in the treatment of cancer pain in the advanced breast cancers with bone metastases. Methods： A total of 80 patients with various degrees of bone pain due to multiple metastases of breast cancer were treated with ^89Sr combined with ^99Tc-MDP. ^89Sr was given intravenously at 4mCi on day 1 during the 3-month schedule. After 7 days, ^99Tc-MDP was given at 22 rag/day on days 1-10 during the 1-month schedule, for 3 to 6 months. Results： The effective rate of relieving pain was 83.75%. The effective rate of curing bone metastases was 81.25%. So there was a significant improvement in the quality of life of the patients. Conclusion： ^89Sr combined with ^99Tc-MDP are effective in the treatment of cancer pain in the breast cancers with bone metastasis, and can obviously repair the bone destruction caused by metastases, thereby improving the quality of life in advanced breast cancer patients with bone metastases.

Long-term Efficacy and Safety of Pamidronate Disodium in Treatment of Bone Metastases in Breast Cancer

Objective： To evaluate the long-term efficacy and safety of pamidronate disodium in patients with bone lesions secondary to advanced breast carcinoma. Methods： A retrospective chart review was conducted of 62 patients receiving intravenous pamidronate disodium for metastatic breast cancer. The proportion of patients experiencing at least one skeletal related event （SRE） after 12 months of therapy was determined. Results： The proportion of patients who had an SRE was 29.00% （18 individuals） and the median time to first event was greater than 350 days. Radiotherapy（ll individuals）and pathologic fracture（6 individuals）were the most frequent type of SRE, while cord compression（1 individuals） and hypercalcaemia（0 individuals） were rare. A total of 37 individuals had transient hypocalcaemia without any clinical symptom. No significant creatinine abnormalities were encountered. There were no clinically relevant changes of calcium ,phosphate and creatinine before and after therapy. Conclusion： Long-term treatment with pamidronate disodium significantly reduces and delays skeletal morbidity from osteolytic metastases . Prolonged therapy was well tolerated. This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase llI clinical trials.

Palliative radiotherapy for bone metastases from lung cancer: Evidence-based medicine?

To review current recommendations for palliative radiotherapy for bone metastases secondary to lung cancer, and to analyze surveys to examine whether global practice is evidence-based, English language publications related to best practice palliative external beam radiotherapy(EBRT) for bone metastases(BM) from lung cancer were sought via literature search(2003-2013). Additional clinical practice guidelines and consensus documents were obtained from the online Standards and Guidelines Evidence Directory. Eligible survey studies contained hypothetical case scenarios which required participants to declare whether or not they would administer palliative EBRT and if so, to specify what dose fractionation schedule they would use. There is no convincing evidence of differential outcomes based on histology or for spine vs non-spine uncomplicated BM. For uncomplicated BM, 8Gy/1 is widely recommended as current best practice; this schedule would be used by up to 39.6% of respondents to treat a painful spinal lesion. Either 8Gy/1 or 20Gy/5 could be considered standard palliative RT for BM-related neuropathic pain; 0%-13.2% would use the former and 5.8%-52.8% of respondents the latter(range 3Gy/1-45Gy/18). A multifraction schedule is the approach of choice for irradiation of impendingpathologic fracture or spinal cord compression and 54% would use either 20Gy/5 or 30Gy/10. Survey results regarding management of complicated and uncomplicated BM secondary to lung cancer continue to show a large discrepancy between published literature and patterns of practice.

Bone metastases from primary hepatocellular carcinoma simulating multiple myeloma

A 65-year-old man presented with bone pains and anemia. Skull X-ray revealed multiple osteolytic lesions. The pa- tient was evaluated for multiple myeloma but detailed workup revealed the diagnosis of primary hepatocellular carcinoma (HCC) with osteolytic bone metastases. Thus, bone metastases due to HCC, although rare, should be considered in patients presenting with bone pains due to os- teolytic lesions.

Etiologies of Bone Metastases at the Rheumatology Department (UTH) of Abidjan

Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descriptive, 11-year retrospective study (January 1, 2006 to December 31, 2016) of inpatient records of bone metastases. The diagnosis was made on clinical (bone signs), radiological (osteolysis, bone condensation) and sometimes histological basis. Result: Eighty out of 6, 1111 inpatients suffered from bone metastasis with a hospital frequency of 1.30%. The average age was 60.74 years (range 26 to 81 years). Men were predominant (53 men for 27 women) with a sex ratio of 1.96. The main complaints were pain (97.6%). chronic (90%), severe (73.8%), inflammatory (93.8%). There was sometimes a neurological complication: a motor deficit (21.3%), sensitive (13.8%). These symptoms were associated with fever (56.3%) and altered general state (85%). Bone metastases have been revealing in the vast majority of cases (93.75%);the primary cancer was known only in 5 patients (prostate = 2, breast = 2 and cervix = 1). Bone condensation (61.3%), osteolysis (50%) and mixed lesions (7.5%) where the main radiological lesions observed. The primary tumors were: prostatic (50%), pulmonary (18.8%), mammary (11.3%), uterine (5%), renal (2.5%), hepatic (2.5%), bladder (1.3%) and adrenal (1.3%). Conclusion: Bone metastases affect mostly the elderly;inflammatory spinal pain is the main symptom. Bone condensation is the most common radiologic lesion. The prostate, breast and lungs are the main primary tumors.

Uncommon Bone Metastases of the Hand

Bone metastases are common and occur in several types of cancer. But when they occur in rare localizations, such as in the hand, they can be the source of a diagnostic and prognostic problem. We report two cases of bone metastases occurring in the hand. The objective of our work is to make the reader think of the diagnosis of metastases in front of a bone lesion in the hand despite its rarity and its occurrence in a patient without pathological history or is followed-up for a cancer which was declared cured or under treatment. Both patients presented with painful swelling, the first one at the 3rd finger and the other one at the 3rd metacarpal. In the first case, bone metastasis revealed the existence of the cancer of origin, and in the second, it was diagnosed in a known patient with cancer. Bone biopsy and histological examination confirmed the diagnosis. Treatment at this advanced stage of the cancerous disease is almost always palliative because, in part, of the aggressiveness of bone metastases. A rapid diagnosis of acrometastases is mandatory in order to avoid a delay in treatment. They are characterized by a pejorative prognosis. Pain control is essential in these types of patients.

Management of Painful Bone Metastases: The Interaction between Radiation Therapy and Zoledronate

Background: Advanced cancers frequently metastasize to bone, and the presence of bone metastases is the most common cause of cancer-related pain. Pain management requires a multidisciplinary approach that involves the use of analgesics, bisphosphonates, radiotherapy, chemotherapy, surgery. The aim of our study was to evaluate the enhancement of radiotherapy on painful bone metastases in patients treated also with bisphosphonates. Materials and Methods: We analyzed the differences in benefit on pain and on quality of life comparing two groups of treatment. The first group comprised 104 patients treated with Radiotherapy (RT), the second one included 50 patients treated with radiotherapy associated to zoledronic acid (RT + Z). All patients completed before, during and after treatment, a questionnaire that rated the grade of pain, the pharmacological type of analgesic therapy and patient’s performance status. For each patient a total score was calculated, from a minimum value of 0% to a maximum of 20%, then expressed as a percentage. Patients were classified as responder if at the follow-up reported a reduction of over 20% of the initial score, no-change if there was a reduction of between 0% and 20%, progression if there was an increasing of the score. Results: In the group RT + Z we found fewer patients that started radiation therapy with severe pain (16% vs 32%), no patient had pain of grade 10, and a higher proportion of asymptomatic patients (12% vs 4%) was observed. In the RT alone group a higher percentage of patients started treatment assuming strong opioid more than once a day (26% vs 24%) and a reduction in number of these patients was about 14% compared with the reduction of 23.6% observed in the group RT + Z. Furthermore an increased total score was calculated only in the 6% of patient belonged to group RT alone. Finally, in the group RT + Z responder patients are 52%, compared to 36% of the RT group, non-responder were 36% versus 60% in the RT. The risk of adverse events (Pz) in the RT + Z was Pz = 0.36, with an odds (Oz) equal to 0.56, while the risk of adverse events (Pc) in the RT group was Pc = 0.60 with an odds (OC) of 1.5. The odds ratio was OR = 0.37, showing a value in favor of treatment RT + Z. Conclusions: In our retrospective observational study it is relevant a clear potentiation of benefit effects related to palliative radiation therapy in patients receiving also bisphosphonate therapy, so obtaining a better control over pain, a decreased need for pain relief and consequently an improved quality of life.

Pain relief by palliative radiotherapy in patients with advanced bone metastases

Objective: To compare 3 local field radiation therapies for bone metastases to determine the strategy producing the best results. Methods: Among 104 patients with bone metastases, 30 patients were given 8 Gy in single fraction, 31 given 20 Gy in 5 fractions, 43 given 40 Gy in 20 fractions. Results and Conclusion: The method of 40 Gy in 20 fractions had a higher pain relief rate and a lower pain relapse rate, suggesting that large-dose fractioned treatment regimen is more appropriate for patients with bone metastasis.

Correlation Study between Skeletal Scintigraphy and CT Scan in Diagnosing Bone Metastases

A retrospective study for 98 patient suspected to bone scan at department of radiology take place, to find out which imaging modality is more sensitive between computed tomography (CT) and bone scan;age group of patient was from 1 year to 90 year, the highest Site of Metastases for both Bone scan & CT was at vertebra with 31%, and the positive finding was also 31% for bone scan, while for CT the highest Site of Metastases was at forearm with 34%, and the sensitivity for CT was 44%, and 56% for bone scan. The study recommends that patients with bone metastases are kindly recommended to bone scan investigation rather than CT scan.

Clinical features and management of prostate cancer with bone metastases:the first report of our Institute

Objective:To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer.Methods:A retrospective study with a total of 128 prostate cancer(Pca) was performed from 2000 to 2005,in our institute.We analyzed the clinical features and outcomes of patients with bone metastases and the data and follow-up of 63 bone metastases was collected by one registrar.Cochran Armitage trend test was used for statistic analysis and a P-value of < 0.05 was taken as statistically significant.Results:The mean age was 73(range 55 to 87) years.The PSA level was from 0.083 ng/mL to 6462 ng/mL.Bone metastases morbidity had good relationship with PSA level.With the mean follow up of 30(range 6 to 72) months for 52/63(82.5%) patients,15(28.8%) died from Pca with a mean survival of 21 months and 1 patient with PSA less than 4 ng/mL at the time died from cerebrovascular suddenness 6 months post-treatment.Conclusion:The early effect of endocrine treatment for bone metastases is obvious,and palliative prostatectomy is satisfactory and able to improve the quality of life rapidly for patients with obstructive symptoms.

The role of radioisotopes for the palliation of bone pain flrOm bone metastases

Bone metastasis occurs as a result of a complex pathophysiologic process between host and tumor cells leading tO cellular invasion,migration adhesion,and stimulation of osteoclastic and osteoblastic activity.Several sequences occur as a result of osseous metastases and resulting bone pain Can lead to significant debilitation.Pain associated with osseous metastasis is thought to be distinct from neuropathic or inflammatory pain.Several mechanisms,such as invasion of tumor cells,spinal cord astrogliosis. and sensitization of nervous system,have been postulated to cause pain.Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates.These drugs are associated with side effects,and tolerance to these agents necessitates treatment with other modalities.Bisphosphonates act by inhibiting osteoclast—mediated resorption and have been increasingly used in treatment of pain- ful bone metastasis.While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions,bone-seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions.32P has been used for over 3 decades in the treatment of multiple osseous metastases.The myelosuppression caused by this agent has led to the development of other bone-seeking radiopharmaceuticals.including 89SrCl.and 153Sm-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP).89Sr is a bone-seeking radionuclide.whereas 153Sm—EDTMP is a bone—seeking tetraphosphonate;both have been approved by the Food and Drug Administration for the treatment of painful osseous metastases.While both agents have been shown to have efficacy in the treatment of painful osseous metastases from prostate cancer,they may also have utility in the treatment of painful OSSEOUS metastases from breast cancer and perhaps from non—small cell lung cancer.This article illustrates the salient features of these radiopharmaceuticals,including the approved dose,method of administration,and indications for use.

RADIONUCLIDE WHOLE BODY BONE IMAGING IN THE DIAGNOSIS OF SKELETAL METASTASES

Of 628 patients with extra-osseous malignancies diagnosed by surgery and/or pathology, 207 (33.0%) were identified as having skeletal metastasis by bone imaging. There was statistical significant difference in the incidence of metastasis in different malignancies (P<0.02). The metastatic rates of nasopharyn-geal, lung, prostate and breast cancers were higher than gastrointestinal, kidney, and other malignancies. There was significant differences in the different sites of skeletal metastasis (P<0.01). They were thorax, spine, pelvis, limbs and skull in order of incidence. Solitary metastatic rate was 15.9%. Biopsy is advised for patients suspected to have metastatic disease but with only one single 'hot spot' in skeletal imaging, particularly in the rib.